Low miR-182-5p expressing extracellular vesicles derived from human bone marrow stromal cells of subjects with steroid-induced osteonecrosis of the femoral head aggravate disease progression.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a refractory, progressive disease. However, the underlying mechanisms which aggravate femoral head necrosis remain unclear. Extracellular vesicles (EVs) act as molecular carrier in intercellular communication. We hypothesize that EVs derived from human (h) bone marrow stromal cells (BMSC) resident in SONFH lesion areas promote the pathogenesis of SONFH. In the present study, we determined the modulatory effects of SONFH-hBMSCs derived EVs on the pathogenesis of SONFH in vitro and vivo. We found that the expression of hsa-miR-182-5p was down regulated in SONFH-hBMSCs and EVs isolated from those hBMSCs. After tail vein injection, EVs isolated from hBMSCs transfected with hsa-miR-182-5p inhibitor, aggravated femoral head necrosis in the SONFH mouse model. We conclude that miR-182-5p regulates bone turnover in the SONFH mouse model via targeting MYD88 and subsequent up regulation of RUNX2 expression. We further assume that EVs derived from hBMSCs resident in SONFH lesion areas aggravate femoral head necrosis by down regulating miR-182-5p secreted from hBMSC located outside these lesions. We suggest that miR-182-5p could provide a novel target for future therapeutic approaches to treat or prevent SONFH. This article is protected by copyright. All rights reserved.